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Saturday 19 October 2019
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Advanced management solutions for calcified lesions

The incidence of coronary, peripheral artery (CAD and PAD) and cerebrovascular diseases is rising in the western world, within an ageing population with comorbidities such as diabetes mellitus, renal failure and obesity. Despite advances in pharmacological treatment, many patients with CAD and PAD require invasive treatment to reduce the symptoms of angina or claudication, salvage myocardial or peripheral muscle, and prevent cardiac death or amputation with subsequent disability in those presenting with acute coronary syndromes (ACS) or critical limb ischaemia (CLI), respectively. For both CAD and PAD, endovascular techniques are widely accepted as first-choice treatment options in most patients. This is attributed to significant technological advances over the last decades. However, in patients with severely calcified or/and chronically totally occluded (CTO) coronary or peripheral lesions, antegrade wire passage may be difficult due to the presence of severe calcification in the area of the proximal cap of the occlusion. In addition, even in cases of successful antegrade or retrograde wire passage, standard interventional treatment options, such as balloon angioplasty, drug-coated balloon (DCB) angioplasty and stent placement may fail. In such cases, advanced techniques may become necessary for tackling such complex and calcified lesions. Advanced age, diabetes mellitus and renal disease, especially chronic haemodialysis, have all been associated with increased coronary and peripheral artery calcification, increasing the need for advanced endovascular techniques beyond balloon angioplasty and stent placement in such patients.  

Complex and calcified coronary lesions

Despite modern coronary drug-eluting stent (DES) technologies, calcified coronary lesions remain a great challenge in interventional cardiology. Thus, severe and especially concentric calcification is associated with inadequate balloon expansion and recoil after balloon angioplasty and with failure to deliver a stent or with suboptimal DES expansion, which is a predictor for both periprocedural complications and stent failure in the long-term due to stent thrombosis or in-stent restenosis.1 With the introduction and implementation of adjunctive techniques, such as rotational atherectomy, scoring balloon angioplasty and recently orbital atherectomy and intravascular lithotripsy, the endovascular treatment of such severely calcified lesions has become increasingly feasible, more predictable and therefore safer. 

Techniques for lesion crossing 

Methods for facilitating crossing of complex lesions, include the use of microcatheters, extension catheters to increase back-up support, over-the-wire balloons, as well as the use of large 7F or 8F support catheters and of anchor balloon support techniques.2
 
Non-compliant, cutting and scoring balloons 
After successful crossing of calcified coronary lesions with a guide wire, the use non-compliant balloons at high pressures is necessary to predilate such lesions. However, lesions with severe concentric calcification may become resistant even to non-compliant balloons despite inflation at high pressures. In addition, the use of high pressures in such stiff calcified lesions may cause dissection or even coronary rupture.3
 
In cases where non-compliant balloons cannot properly expand, the use of scoring balloons may facilitate better lesion preparation. Such balloons are surrounded by external nitinol spiral scoring wires and are more flexible and better deliverable than previously used cutting balloons. Dilatation using such balloons creates a ‘scoring’, that is, a calcium fracturing’ effect into the calcified and fibrotic tissue of the lesion through a focused transmission force, applied by the very distal portion of these elements. Generally, scoring balloons may be successful for the treatment of moderately to severe calcified coronary lesions.
 
Rotational atherectomy 
Rotational atherectomy has been introduced in the field of interventional cardiology about three decades ago, primarily aiming at mechanical debulking of severely fibrocalcific atherosclerotic plaque. This technique provides ablation of fibrocalcific plaque components through a high-speed rotating burr (~140,000–180,000rpm), whereas non-fibrocalcific, elastic components are spared by deflecting away from the burr. Current guidelines recommend the use of rotational atherectomy for plaque modification before adjacent treatment with balloon angioplasty and DES placement. Although a recent randomised trial was not able to demonstrate a long-term benefit for the use of rotational atherectomy in complex calcified coronary lesions, this technique is widely accepted as the default strategy for such lesions prior to DES placement.4 An example of a severely calcified lesion in the circumflex artery of a patient treated with rotational atherectomy prior to the implantation of three DES is shown in Figure 1.
 
Figure 1
Figure 1: Images of an 82-year old female patient, with history of 3 vessel CAD and prior bypass surgery, who was referred to our department with non-ST elevation myocardial infarction. Coronary angiography showed a patent left mammary graft to the left ascending coronary artery, a functionally occluded right coronary artery (not shown) and multiple tight lesions in the circumflex coronary artery (blue arrows in A). During prior bypass surgery nine years ago, a graft could not be inserted to the circumflex artery due to severe calcification. We therefore proceeded with rotational atherectomy of the circumflex artery (B–E), which was followed by the implantation of three DES in the circumflex and in the left main coronary artery, with a good final angiographic result in F. 
 
Orbital atherectomy 
With orbital atherectomy, an eccentrically mounted diamond-coated crown that orbits 360 degrees within the vessel is used for circumferential plaque removal. Calcific plaque tissue can be removed in this way without causing vessel wall trauma. In contrast to rotational atherectomy, which is limited by the size of the catheter tip or burr size, the debulked area can be increased by increasing the rotational speed of the eccentrically mounted crown. Like rotational atherectomy, orbital atherectomy is also recommended in severely calcified coronary lesions to provide plaque modification prior to balloon angioplasty and DES placement. Orbital atherectomy was approved in 2013 in the US and has approved in Europe in 2018. This technique is available for both coronary and peripheral vessels. 
 
Intracoronary lithotripsy
Intravascular lithotripsy uses pulsatile mechanical energy in order to disrupt calcific lesions, similar to extracorporeal lithotripsy used to disrupt kidney stones. This is facilitated by a balloon angioplasty catheter, containing a series of electrohydraulic lithotripsy emitters, which are used to convert electrical energy to transient acoustic pressure pulses. The single use balloon catheter is connected to a generator, which enables the delivery of prespecified pulse per treatment. First human studies demonstrated the safety and high efficacy of the lithotripsy catheter balloon angioplasty for the treatment of heavily calcified lesions, exhibiting a low rate of major adverse events during 30 days of follow-up.5 In this regard, high resolution optical coherence tomography revealed multiple calcium fractures, enabling area gain for the delivery and expansion of DES as the mechanism of action. This technique is available for both coronary and peripheral vessels.

Complex and calcified peripheral lesions

Due to recent technological advances a minimally invasive endovascular approach is in the meanwhiles widely accepted for the treatment of symptomatic patients with PAD. Commonly used techniques include plain balloon angioplasty, DCB angioplasty, bare metal stents and drug-eluting stents. All these devices have been successfully used to treat claudication symptoms and have achieved limb salvage in CLI patients.6,7
 
Endovascular approaches, however, may be compromised by severe calcification. Calcification may be the reason for a poor primary outcome due to early recoil or extensive flow-limiting dissections after high-pressure angioplasty.8 Such mechanical effects increase the probability of the need for bailout stent placement, which even with modern dedicated stent devices is associated suboptimal long-term patency, especially in moving vessel zones.9 With the use of percutaneous plaque modification and debulking techniques based on atherectomy however, such calcified lesions can be tackled more easily after removal or fragmentation of atherosclerotic plaque. More homogeneous balloon expansion at lower pressures can be achieved in this way, which reduces barotrauma while facilitating better drug delivery to the vessel wall during DCB angioplasty, and in many cases obviating the need for stent placement. Some of the techniques available for wire passage with CTO lesions, as well as devices available for debulking and lesion preparation in heavily calcified peripheral arteries, are described below.

Techniques for lesion crossing 

Similar to coronary CTO, methods for facilitating crossing of peripheral CTO, include the use of support catheters and the puncture of the distal superficial artery, crural or pedal arteries. Such distal puncture techniques may more easily facilitate passage of the occlusive lesion, because like with coronary CTO the distal cap is usually less calcified and therefor easier to penetrate compared to the proximal cap of the occlusive lesion.10
 
Scoring balloons 
Like in coronary arteries, scoring balloons can be used in moderately to heavily calcified peripheral lesions, facilitating improved lesion preparation. In this regard, data from the Heidelberg PANTHER registry indicate that treatment of calcified femoropopliteal lesions with the AngioSculptTM scoring balloon is safe and is associated with a high technical success rate and a primary patency rate of 81.2% at 12 months of follow-up.11 
 
Directional atherectomy 
With directional atherectomy, carbide rotating cutter blades are used to cut and remove atherosclerotic tissue. As implied by the name of this technique, the atherectomy device can be guided to the target lesion and rotated in the preferred direction. Thus, directional atherectomy is an optimal technique for the treatment of eccentric lesions. The resected tissue is collected in a nose cone, which must be repeatedly emptied when several passages are necessary. Because no aspiration mechanism is involved, the use of a distal protection filter is mandatory with this device. The safety and efficacy of directional atherectomy has been previously investigated in prospective multicentre studies. One of these studies, the DEFINITIVE AR trial, sought to compare upfront directional atherectomy combined with DCB versus a DCB-only strategy in a randomised setting.12 In this study, combined treatment with atherectomy and DCB was effective and safe; however, no added value was observed in comparison with a DCB-only strategy at one year of follow-up. 
 
Rotational atherectomy 
With rotational atherectomy techniques, tissue is concentrically excised using specially designed rotating tips or burrs. The size of the tips or burrs therefore determine the extent of luminal gain. Several systems are available for rotational atherectomy, including the Rotarex®S system (Straub Medical), the Jetstream Atherectomy device (Boston Scientific) and the Phoenix device (Philips Volcano), the latter combining rotational and directional features. The Rotarex®S (Straub Medical, Wangs, Switzerland) consists of an external drive system, connected with the Rotarex®S catheter system. A helix inside the catheter transmits the rotation to the catheter head, which rotates with 10,000 rpm, thus creating a negative suction force. This enables the collection of fragmented tissue into an external bag. Jetstream, on the other hand, is available with two types of catheters, one equipped with a single set of front cutting blades and one with a second set of larger blades to increase the capability of upfront debulking.
 
This device also provides continuous aspiration and removal of the excised tissue. The Phoenix device is available in sizes of 1.8mm, 2.2mm and 2.4mm. The 2.4-mm catheter possesses a deflecting tip, facilitating a combined directional and rotational atherectomy modus. The Phoenix device possesses a front cutter, which is rotated at high speed (10,000–12,000 rpm), also creating a strong suction force, which allows continuous aspiration of the fragmented plaque components into an external bag. We and others recently demonstrated the safety and efficacy of the Phoenix atherectomy device in femoropopliteal and below-the-knee lesions.13,14 An example of a severely calcified lesion in the common femoral artery of a patient with critical limb ischaemia treated with Phoenix atherectomy, combined with scoring balloon angioplasty and DCB and without stent placement is shown in Figure 2.
 
Figure 2
Figure 2: Digital subtraction angiography (DSA) images of an 84-year old female patient, with history of severe PAD, who was referred to our department with critical limb ischaemia, Rutherford stage 6. Baseline DSA images demonstrated a tight, heavily calcified lesion of the right common femoral artery (blue arrows in A) and a chronically occluded superficial femoral artery. Phoenix atherectomy was performed in B (blue arrows in B showing bilateral calcifications), combined by AngioSculptTM scoring balloon (C) and Stellarex DCB, with a good angiographic result in D.  

Conclusions

With an increasing number of patients suffering from diabetes mellitus and renal failure or haemodialysis, the proportion of patients with complex and calcified coronary and peripheral lesions is already high and is expected to rise even more in the next decades. In addition, with an increasing number of cardiopulmonary and cerebrovascular comorbidities, the proportion of patients at high risk for open cardiac or vascular surgery is also expected to rise in coming years, thus further establishing the role of coronary and peripheral endovascular procedures as the first option for the treatment of such patients. In order to facilitate treatment of such complex fibrocalcific lesions however, advanced treatment options, such as high-pressure and scoring balloon angioplasty together with directional, rotational or orbital atherectomy techniques, have become mandatory and implementation of such techniques will be crucial to improve both acute success and long-term outcomes.
 
Many FDA-approved atherectomy devices are currently available in the market for coronary and/or for peripheral use. From the practical point of view, such devices are readily widely accepted by interventional cardiologists and angiologists. Considering the availability of diverse scoring balloon and atherectomy devices, it may be advisable to first gain expertise in the use of a single device, optimally applicable for both coronary and peripheral vessels with due attention to patient selection and lesion characteristics. 
 
References
1 Dangas GD et al. In-stent restenosis in the drug-eluting stent era. J Am Coll Cardiol 2010;56(23):1897–907. 
2 Kassimis G et al. How should we treat heavily calcified coronary artery disease in contemporary practice? From atherectomy to intravascular lithotripsy. Cardiovasc Revascularization Med Mol Interv 2019; pii: S1553-8389(19)30040-5. 
3 Seth A et al. Expert opinion: Optimising stent deployment in contemporary practice: The role of intracoronary imaging and non-compliant balloons. Interv Cardiol Lond Engl 2017;12(2):81–4. 
4 Abdel-Wahab M et al. High-speed rotational atherectomy before paclitaxel-eluting stent implantation in complex calcified coronary lesions: the randomized ROTAXUS (Rotational Atherectomy Prior to Taxus Stent Treatment for Complex Native Coronary Artery Disease) trial. JACC Cardiovasc Interv 2013;6(1):10–19. 
5 Ali ZA et al. Optical coherence tomography characterization of coronary lithoplasty for treatment of calcified lesions: First description. JACC Cardiovasc Imaging 2017;10(8):897–906. 
6 Fakhry F et al. Endovascular revascularization and supervised exercise for peripheral artery disease and intermittent claudication: A randomized clinical trial. JAMA 2015;314(18):1936–44. 
7 Agarwal S, Sud K, Shishehbor MH. Nationwide trends of hospital admission and outcomes among critical limb ischemia patients: From 2003–2011. J Am Coll Cardiol 2016;67(16):1901–13. 
8 Fitzgerald PJ, Ports TA, Yock PG. Contribution of localized calcium deposits to dissection after angioplasty. An observational study using intravascular ultrasound. Circulation 1992;86(1):64–70. 
9 Cambiaghi T et al. Fracture of a Supera interwoven nitinol stent after treatment of popliteal artery stenosis. J Endovasc Ther Off J Int Soc Endovasc Spec. 2017;24(3):447–9. 
10 Giusca S et al. Comparison of ante- vs. retrograde access for the endovascular treatment of long and calcified femoropopliteal occlusive lesions. LINC Congress In Leipzig; 2019. 
11 Lugenbiel I et al. Treatment of femoropopliteal lesions with the AngioSculpt scoring balloon – results from the Heidelberg PANTHER registry. VASA Z Gefasskrankheiten 2018;47(1):49–55. 
12 Zeller T et al. Directional atherectomy followed by a paclitaxel-coated balloon to inhibit restenosis and maintain vessel patency: Twelve-month results of the DEFINITIVE AR Study. Circ Cardiovasc Interv 2017;10(9): pii: e004848. 
13 Davis T et al. Safety and effectiveness of the Phoenix Atherectomy System in lower extremity arteries: Early and midterm outcomes from the prospective multicenter EASE study. Vascular 2017;25(6):563–75. 
14 Giusca S et al. Endovascular treatment with the Phoenix Atherectomy System in patients with chronic limb ischemia. A series of seventy-four consecutive patients. LINC Congress In Leipzig; 2019.